1-70421416-A-T

Variant names:

• chr1-70421416-A-T
• rs672203
• NM_001902.6:c.347-150A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001902.6(CTH):​c.347-150A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 0 publications found

Genes affected

CTH (HGNC:2501): (cystathionine gamma-lyase) This gene encodes a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathione derived from methionine into cysteine. Glutathione synthesis in the liver is dependent upon the availability of cysteine. Mutations in this gene cause cystathioninuria. Alternative splicing of this gene results in three transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

CTH Gene-Disease associations (from GenCC):

• cystathioninuria

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTH	NM_001902.6	c.347-150A>T		intron_variant	Intron 3 of 11	ENST00000370938.8	NP_001893.2
CTH	NM_001190463.2	c.251-150A>T		intron_variant	Intron 2 of 10		NP_001177392.1
CTH	NM_153742.5	c.347-150A>T		intron_variant	Intron 3 of 10		NP_714964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTH	ENST00000370938.8	c.347-150A>T		intron_variant	Intron 3 of 11	1	NM_001902.6	ENSP00000359976.3
CTH	ENST00000346806.2	c.347-150A>T		intron_variant	Intron 3 of 10	1		ENSP00000311554.2
CTH	ENST00000411986.6	c.251-150A>T		intron_variant	Intron 2 of 10	2		ENSP00000413407.2
CTH	ENST00000464926.1	n.395-150A>T		intron_variant	Intron 2 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 644940 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 340344

African (AFR) AF: 0.00 AC: 0 AN: 16168

American (AMR) AF: 0.00 AC: 0 AN: 29456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19034

East Asian (EAS) AF: 0.00 AC: 0 AN: 31938

South Asian (SAS) AF: 0.00 AC: 0 AN: 58418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2458

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 412078

Other (OTH) AF: 0.00 AC: 0 AN: 32762

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.56
PhyloP100		3.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs672203; hg19: chr1-70887099;